Approach to the patient: precision medicine-guided evaluation and treatment of acromegaly.

Acromegaly is a heterogeneous disease in which delayed biochemical control remains common despite the availability of multiple therapeutic options. Traditional stepwise medical treatment algorithms often rely on the use of first-generation somatostatin receptor ligands (fgSRLs) as first-line drugs with empirical escalation and trial-and-error approaches, prolonging patients' exposure to hormonal excess. Cluster analyses indicate that overall, 3 main classes of patients with acromegaly representing distinct biological phenotypes can be recognized: (1) young patients with invasive macroadenomas and frequent resistance to fgSRLs; (2) older patients with noninvasive tumors and SRL responsiveness in the majority of them; and (3) patients with intermediate features often requiring combination medical therapy in whom prediction of response is more challenging. From a practical perspective, biomarker-guided treatment selection based on T2-weighted magnetic resonance imaging signal intensity, the short acute octreotide test, and tumor immunohistochemistry, following the strategy validated in the ACROFAST study, is applicable in clinical practice. It allows prompt biochemical control and tumor volume reduction, a rationale leading to superior effectiveness performance than the classic sequencing therapy involving the universal utilization of fgSRLs as first option. In the era of integrative and participative medicine, such a protocol enables the early identification of most patients unlikely to respond to fgSRLs, thus supporting timely initiation of pegvisomant, pasireotide, or combination therapy, and the achievement of hormonal control in nearly 80% of patients. Conclusion Precision medicine has become a practical reality in acromegaly. A biomarker-guided strategy improves therapeutic efficiency and should be incorporated into contemporary clinical practice.